P832: CLINICAL OUTCOMES AND IMMUNE RESPONSES TO SARS-COV-2 VACCINATION IN PATIENTS WITH SEVERE APLASTIC ANEMIA
Authors: R. Rajput, X. Ma, K. L. Boswell, M. Gaudinski, E. M. Groarke, J. Lotter, O. Rios, I. Darden, C. O. Wu, R. A. Koup, N. S. Young, B. Patel
Journal: HemaSphere (2022)

Background: Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 has led to significant morbidity and mortality in patients with hematological disease. Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder that presents with pancytopenia and a hypocellular marrow due to immune-mediated destruction of hematopoietic stem cells (HSC). Patients are at high risk for infection due to neutropenia and treatment with immunosuppressive therapy (IST). Acute COVID-19 infection has been reported to cause worsening underlying marrow failure and death in unvaccinated SAA patients. Patients with SAA are often not vaccinated to protect against routine viruses due to concerns of ineffective protective specific antibody response to viral antigens and potential pathogenic global immune system activation. To date, the clinical impact and efficacy of COVID-19 vaccination in SAA has not been described. Aims: Assess the impact of SARS-CoV-2 vaccination on SAA disease status and to determine the humoral and cellular response to vaccination. Methods: SAA treated with IST including horse antithymocyte globulin (h-ATG), cyclosporine (CSA), and eltrombopag (EPAG) at the National Institute of Health with confirmation of SARS-CoV-2 vaccination between January and November 2021 were included. Current SAA disease status at the time of vaccination was recorded as complete response (CR), partial response (PR) and non-response (NR). Univariate analysis was performed using the Student paired t-test to compare available blood counts. Peripheral mononuclear blood cells (n=27) and serology (n=12) after completion of vaccination series were analyzed to assess cellular and humoral response, respectively. Results: Blood samples from fifty patients with SAA with median age of 42 years (9-78), 29 females, and 21 males, were studied. At time of vaccination, 15 patients (30%) were receiving CSA. Forty-seven of 50 (94%) of patients did not have any changes in disease status after vaccination. Among 40 patients with available data 3 months prior to and after completion of vaccination series, there was no significant difference in HGB (p=0.52) PLT (p=0.67), ANC (p=0.98), and ALC (p=0.42; Figure 1A-C). Relapse after vaccination, defined as progressive and substantial decline in blood counts, was noted in 3 (6%) cases. All 3 relapsed patients were deemed weak PR at time of vaccination (PLT < 50 K/μL) and were 6 months, 3 years, and 4 years from initial IST. Two of the 3 patients received an initial Pfizer inoculation and did not receive the second dose because of declining blood counts. Relapse occurred 4 weeks after completion of a full Moderna series in the third patient, who had demonstrated a decline in counts 6 months prior to vaccination. Vaccinated SAA patients all had adequate antibody production to the SARS-CoV-2 spike protein. They also exhibited a CD4+ Th1 dominant response, similar to healthy controls, even when receiving CSA at time of vaccination (Figure D). CD8+ responses to vaccination were observed, but patients with SAA appear to have qualitatively blunted responses compared to controls. Image:Summary/Conclusion: SARS-CoV-2 vaccination in SAA may result in transient decline in blood counts but true relapse is rare. Relapse may be more likely in patients whose blood counts are declining prior to vaccination. Appropriate humoral and cellular responses are seen in patients with SAA. A risk versus benefit assessment to vaccinate against SARS-CoV-2 in SAA may be warranted in patients with weak partial response to initial therapy or whom have clinical or laboratory evidence suggestive of active disease.